TWI840226B - Automatic sample preparation system - Google Patents
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- 238000002360 preparation method Methods 0.000 title claims abstract description 108
- 238000000605 extraction Methods 0.000 claims abstract description 134
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Abstract
Description
本發明係關於自動化樣品準備系統。 The present invention relates to an automated sample preparation system.
在現代疾病診斷、藥物開發、環境檢測、食品檢測、刑事鑑定、學術研究等領域中常會需要利用到生物活性物質，例如細胞、蛋白質、遺傳物質等。其中，遺傳物質為生命基本物質之一，包含核糖核酸(簡稱RNA)及去氧核醣核酸(簡稱DNA)，其廣泛存在於所有動植物、微生物、病毒內。隨著生物技術發展，已能夠將遺傳物質從生物體中萃取出來並進行後續分析與應用。目前已發展出能夠自動化將遺傳物質從檢體中萃取出來的設備。然而，生物檢體的形式相當多樣，依據採樣方式不同，生物檢體可包含如血液、唾液、尿液之體液、如福馬林固定石蠟包埋(Formalin-fixed paraffin-embedding，FFPE)樣品之固體蠟塊、培養細胞、菌落、鼻拭子等。這些多樣的生物檢體在進行萃取之前必須經過前處理，以成為適用於自動化萃取設備的樣品，才能進行萃取。萃取出來的遺傳物質常需要進行如聚合酶連鎖反應(Polymerase chain reaction，PCR)之擴增反應。並且，依據後續分析與應用，遺傳物質在進行擴增反應前有時需要進行定量分析。 In modern disease diagnosis, drug development, environmental testing, food testing, criminal forensics, academic research and other fields, biologically active substances such as cells, proteins, and genetic substances are often needed. Among them, genetic substances are one of the basic substances of life, including ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), which are widely present in all animals, plants, microorganisms, and viruses. With the development of biotechnology, it has become possible to extract genetic substances from organisms and conduct subsequent analysis and application. At present, equipment that can automatically extract genetic substances from specimens has been developed. However, biological specimens come in a variety of forms. Depending on the sampling method, biological specimens can include body fluids such as blood, saliva, and urine, solid wax blocks such as formalin-fixed paraffin-embedded (FFPE) samples, cultured cells, bacterial colonies, nasal swabs, etc. These various biological specimens must be pre-treated before extraction to become samples suitable for automated extraction equipment before extraction can be performed. The extracted genetic substances often need to undergo amplification reactions such as polymerase chain reaction (PCR). Moreover, depending on the subsequent analysis and application, genetic substances sometimes need to be quantitatively analyzed before amplification reactions.
然而，目前市面上的自動化萃取設備並不包含樣品的前處理，亦不包含後續定量及配製溶液的功能。在樣品前處理、擴增前定量與配製溶液的過程中都需要專業技術人員與額外設備來操作。人為操作不僅耗費時間、人力，亦會產生人為誤差。更重要的是，人為操作會大幅增加的汙染的風險。 However, the automated extraction equipment currently available on the market does not include sample pretreatment, nor does it include the functions of subsequent quantification and solution preparation. Professional technicians and additional equipment are required to operate the sample pretreatment, pre-expansion quantification, and solution preparation. Manual operation not only consumes time and manpower, but also produces human errors. More importantly, manual operation will greatly increase the risk of contamination.
本發明一實施例之自動化樣品準備系統將樣品前處理、萃取、定量、配製溶液整合於一個系統中，由自動化系統取代人為操作可降低時間與人力成本、減少人為操作造成的誤差，更可降低汙染風險。 The automated sample preparation system of one embodiment of the present invention integrates sample pretreatment, extraction, quantification, and solution preparation into one system. Replacing manual operation with an automated system can reduce time and labor costs, reduce errors caused by manual operation, and reduce the risk of contamination.
本發明一實施例提供一種自動化樣品準備系統，包含：樣品準備模組，用以對樣品進行前處理使樣品成為可用於萃取的形態；萃取模組，用以裝設萃取試劑條並利用萃取試劑條從樣品萃取出遺傳物質；置物模組，用以放置盛裝樣品的容器、盛裝萃取完成的遺傳物質的容器及萃取用吸量管尖；擴增前定量模組，用以對萃取完成的遺傳物質進行定量；擴增樣品準備模組，用以將萃取完成的遺傳物質配製成適用於擴增反應的溶液；非萃取用吸量管尖盛裝模組，用以盛裝非萃取用吸量管尖；以及吸量模組，用以移動到置物模組裝設萃取用吸量管尖以在樣品準備模組、萃取模組及置物模組中進行液體混合或移液，或者用以移動到非萃取用吸量管尖盛裝模組裝設非萃取用吸量管尖以在置物模 組、擴增前定量模組及擴增樣品準備模組中進行液體混合或移液；其中萃取模組與置物模組設置於樣品準備模組的相對兩側，擴增前定量模組、擴增樣品準備模組及非萃取用吸量管尖盛裝模組設置於置物模組遠離樣品準備模組的一側。 An embodiment of the present invention provides an automated sample preparation system, comprising: a sample preparation module for pre-treating a sample to make the sample in a form that can be used for extraction; an extraction module for installing an extraction reagent strip and using the extraction reagent strip to extract genetic substances from the sample; a storage module for placing a container for holding a sample, a container for holding an extracted genetic substance, and an extraction pipette tip; a pre-expansion quantitative module for quantitatively measuring the extracted genetic substance; an expansion sample preparation module for preparing the extracted genetic substance into a solution suitable for an expansion reaction; and a non-extraction pipette tip containing module for A non-extraction pipette tip is contained; and a pipette module is used to move to the storage module to install the extraction pipette tip to mix or transfer liquids in the sample preparation module, extraction module and storage module, or to move to the non-extraction pipette tip holding module to install the non-extraction pipette tip to mix or transfer liquids in the storage module, pre-expansion quantitative module and expanded sample preparation module; wherein the extraction module and the storage module are arranged on opposite sides of the sample preparation module, and the pre-expansion quantitative module, the expanded sample preparation module and the non-extraction pipette tip holding module are arranged on the side of the storage module away from the sample preparation module.
根據本發明一實施例的自動化樣品準備系統，將樣品前處理、萃取、擴增前定量、配製擴增溶液整合於一個系統中。自動化樣品準備系統的樣品準備模組除了液體樣品以外，亦可對如蠟塊之固體樣品進行前處理。自動化樣品準備系統的吸量模組可透過來回吸吐的方式使液體進行全面性的混合，相較於攪拌混合，可使液體混合更加均勻，並可避免因攪拌造成碰撞而損壞。自動化樣品準備系統中各模組的排列方式可減少吸量模組在各模組間的移動距離，藉此降低在移動過程中造成汙染或碰撞損壞的風險。藉由將各程序自動化來取代人為操作，可簡化操作、降低時間人力成本、提升效率，且藉由標準化的流程可減少人為誤差、提高可靠性，更重要的是，可大幅降低受到汙染的風險。 According to an automated sample preparation system of one embodiment of the present invention, sample pretreatment, extraction, pre-expansion quantification, and preparation of expansion solution are integrated into one system. In addition to liquid samples, the sample preparation module of the automated sample preparation system can also perform pretreatment on solid samples such as wax blocks. The pipetting module of the automated sample preparation system can comprehensively mix the liquid by aspirating and spitting back and forth. Compared with stirring and mixing, the liquid can be mixed more evenly and collision damage caused by stirring can be avoided. The arrangement of the modules in the automated sample preparation system can reduce the moving distance of the pipetting module between the modules, thereby reducing the risk of contamination or collision damage during the movement process. By automating each process to replace manual operations, operations can be simplified, time and labor costs can be reduced, and efficiency can be improved. Standardized processes can reduce human errors, improve reliability, and more importantly, significantly reduce the risk of contamination.
10:自動化樣品準備系統 10: Automated sample preparation system
100:樣品準備模組 100: Sample preparation module
200:萃取模組 200: Extraction module
210:萃取試劑條 210: Extraction reagent strips
300,300A,300B,300C,300D:置物模組 300,300A,300B,300C,300D: Storage module
400:擴增前定量模組 400: Expand the quantitative module before
500:擴增樣品準備模組 500: Expanded sample preparation module
510:擴增試劑區 510: Expanded reagent area
520:擴增樣品放置區 520: Expanded sample placement area
600:非萃取用吸量管尖盛裝模組 600: Non-extraction pipette tip holder module
700:吸量模組 700: Suction module
710:第一吸量模組 710: First suction module
720:第二吸量模組 720: Second suction module
800:廢棄物收集模組 800: Waste collection module
900:殼體 900: Shell
910:開口 910: Open mouth
920:影像辨識模組 920: Image recognition module
930:紫外光滅菌模組 930: UV sterilization module
A:第一吸量模組的移動範圍 A: The moving range of the first suction module
B:第二吸量模組的移動範圍 B: Moving range of the second suction module
圖1為根據本發明一實施例之自動化樣品準備系統的平面示意圖。 Figure 1 is a schematic plan view of an automated sample preparation system according to an embodiment of the present invention.
圖2為裝設於萃取模組的萃取試劑條的一例。 Figure 2 shows an example of an extraction reagent strip installed in an extraction module.
圖3A為適用於10毫升血清或血漿的置物模組。 Figure 3A shows a storage module suitable for 10 ml of serum or plasma.
圖3B為適用於蠟塊(例如FFPE)的置物模組。 Figure 3B shows a storage module suitable for wax blocks (e.g. FFPE).
圖3C為適用於病毒或血液的置物模組。 Figure 3C is a storage module suitable for viruses or blood.
圖3D為適用於5毫升血清或血漿的置物模組。 Figure 3D shows a storage module suitable for 5 ml of serum or plasma.
於以下實施方式中詳細敘述本發明之詳細特徵及優點，其內容足以使任何熟習相關技藝者了解本發明之技術內容並據以實施，且根據本說明書所揭露的內容、申請專利範圍及圖式，任何熟習相關技藝者可輕易理解本發明相關之目的及優點。以下實施例係進一步詳細說明本發明之觀點，但非以任何觀點限制本發明之範疇。 The detailed features and advantages of the present invention are described in detail in the following implementation methods, and the content is sufficient for any person familiar with the relevant technology to understand the technical content of the present invention and implement it accordingly. According to the content disclosed in this specification, the scope of the patent application and the drawings, any person familiar with the relevant technology can easily understand the relevant purposes and advantages of the present invention. The following embodiments are to further illustrate the viewpoints of the present invention in detail, but do not limit the scope of the present invention by any viewpoint.
請參考圖1，圖1為根據本發明一實施例之自動化樣品準備系統的平面示意圖。根據本發明一實施例，自動化樣品準備系統10包含樣品準備模組100、萃取模組200、置物模組300、擴增前定量模組400、擴增樣品準備模組500、非萃取用吸量管尖盛裝模組600及吸量模組700。萃取模組200與置物模組300設置於樣品準備模組100的相對兩側，擴增前定量模組400、擴增樣品準備模組500及非萃取用吸量管尖盛裝模組600設置於置物模組300遠離樣品準備模組100的一側。此排列方式可減少吸量模組700在各模組間的移動距離，藉此降低在移動過程中造成汙染或碰撞損壞的風險。 Please refer to FIG1 , which is a schematic plan view of an automated sample preparation system according to an embodiment of the present invention. According to an embodiment of the present invention, the automated sample preparation system 10 comprises a sample preparation module 100, an extraction module 200, a storage module 300, a pre-expansion quantitative module 400, an expanded sample preparation module 500, a non-extraction pipette tip holding module 600, and a pipette module 700. The extraction module 200 and the storage module 300 are arranged on opposite sides of the sample preparation module 100, and the pre-expansion quantitative module 400, the expanded sample preparation module 500, and the non-extraction pipette tip holding module 600 are arranged on a side of the storage module 300 away from the sample preparation module 100. This arrangement can reduce the moving distance of the suction module 700 between modules, thereby reducing the risk of contamination or collision damage during movement.
樣品準備模組100用以對樣品進行前處理使樣品成為可用於萃取的形態。所述可用於萃取的形態係指可使用吸量管 吸吐且可與萃取試劑混合的液體形態。樣品可為液體或固體。樣品可包含蠟塊、血液、血漿、血清、唾液、病毒、病原體、細菌或細胞。舉例而言，當樣品需要稀釋時，樣品可在樣品準備模組100進行稀釋，成為可用於萃取的形態。可用於萃取的樣品可經由後述之吸量模組700從樣品準備模組100移動至萃取模組200進行萃取。 The sample preparation module 100 is used to pre-treat the sample so that the sample becomes a form that can be used for extraction. The form that can be used for extraction refers to a liquid form that can be sucked and discharged using a pipette and can be mixed with an extraction reagent. The sample can be liquid or solid. The sample can include wax, blood, plasma, serum, saliva, virus, pathogen, bacteria or cells. For example, when the sample needs to be diluted, the sample can be diluted in the sample preparation module 100 to become a form that can be used for extraction. The sample that can be used for extraction can be moved from the sample preparation module 100 to the extraction module 200 for extraction via the pipette module 700 described later.
樣品準備模組100可包含加熱區，加熱區用以加熱放置於此處的樣品。加熱區的範圍可涵蓋整個樣品準備模組100或涵蓋部分的樣品準備模組100。舉例而言，當樣品為如FFPE之蠟塊時，可將蠟塊放置於樣品準備模組100的加熱區，使蠟塊經由加熱融化成液體，成為可用於萃取的形態。 The sample preparation module 100 may include a heating zone for heating the sample placed therein. The range of the heating zone may cover the entire sample preparation module 100 or a portion of the sample preparation module 100. For example, when the sample is a wax block such as FFPE, the wax block may be placed in the heating zone of the sample preparation module 100 so that the wax block is heated and melted into a liquid, and becomes a form that can be used for extraction.
萃取模組200用以裝設萃取試劑條210並利用萃取試劑條210從樣品萃取出遺傳物質。圖2為裝設於萃取模組的萃取試劑條的一例。萃取試劑條210可具有多個管體連接在一起的結構。在部分管體中可盛裝有用於進行萃取反應的試劑，例如含磁珠緩衝液、裂解液、清洗液、溶析液，另一部分管體可為空管。萃取試劑條210中的試劑可依樣品種類不同而有所不同。萃取試劑條210可部分位於樣品準備模組100。舉例而言，如圖2所示之萃取試劑條210具有最外側兩個空管位於樣品準備模組100，萃取試劑條210的最外側兩個空管可用於盛裝欲進行前處理的樣品。萃取模組200可具有防呆結構。舉例而言，萃取模組200可 具有對應於萃取試劑條210的結構以定位萃取試劑條210，藉此防止裝設錯誤，確保萃取流程正確的進行。 The extraction module 200 is used to install the extraction reagent strip 210 and utilize the extraction reagent strip 210 to extract genetic substances from the sample. FIG2 is an example of an extraction reagent strip installed in the extraction module. The extraction reagent strip 210 may have a structure in which multiple tubes are connected together. Reagents used for extraction reactions, such as magnetic bead buffer, lysis solution, cleaning solution, and elution solution, may be contained in part of the tube, and another part of the tube may be an empty tube. The reagents in the extraction reagent strip 210 may vary depending on the type of sample. The extraction reagent strip 210 may be partially located in the sample preparation module 100. For example, as shown in FIG. 2 , the extraction reagent strip 210 has two outermost empty tubes located in the sample preparation module 100. The two outermost empty tubes of the extraction reagent strip 210 can be used to hold samples to be pre-processed. The extraction module 200 can have a foolproof structure. For example, the extraction module 200 can have a structure corresponding to the extraction reagent strip 210 to position the extraction reagent strip 210, thereby preventing installation errors and ensuring that the extraction process is carried out correctly.
在萃取模組200中可藉由後述之吸量模組700進行液體混合或移液。在裝設有萃取試劑條210的萃取模組200中，可藉由磁珠緩衝液的磁珠吸附樣品中遺傳物質，並藉由吸量模組700吸取管體中的溶液並移動至下一個管體，使樣品依序在萃取試劑條210的各管體移動以進行萃取。在萃取過程中，液體混合可由吸量模組700透過來回吸吐的方式來進行。萃取完成的遺傳物質可經由吸量模組700移動至置物模組300。 In the extraction module 200, liquid mixing or liquid transfer can be performed by the pipette module 700 described later. In the extraction module 200 equipped with the extraction reagent strip 210, the genetic material in the sample can be adsorbed by the magnetic beads of the magnetic bead buffer, and the solution in the tube body can be absorbed by the pipette module 700 and moved to the next tube body, so that the sample moves in each tube body of the extraction reagent strip 210 in sequence for extraction. During the extraction process, liquid mixing can be performed by the pipette module 700 through a back and forth suction and spitting method. The extracted genetic material can be moved to the storage module 300 through the pipette module 700.
置物模組300用以放置盛裝樣品的容器、盛裝萃取完成的遺傳物質的容器及萃取用吸量管尖。盛裝樣品的容器可用於盛裝尚未進行萃取的原始液體樣品。萃取用吸量管尖可裝設於後述之吸量模組700以用於萃取。置物模組300可沿朝向萃取模組200的方向依序放置盛裝樣品的容器、萃取用吸量管尖及盛裝萃取完成的遺傳物質的容器。換言之，盛裝萃取完成的遺傳物質的容器最靠近萃取模組200，可使萃取完成的遺傳物質可以最短距離移動至容器中，藉此降低在移液過程中受到汙染的風險。置物模組300依據不同樣品種類可有不同的結構。舉例而言，圖3A至圖3D為適用於不同樣品的置物模組300，圖3A為適用於10毫升血清或血漿的置物模組300A，圖3B為適用於蠟塊(例如FFPE)的置物模組300B，圖3C為適用於病毒或血液的置物模組 300C，圖3D為適用於5毫升血清或血漿的置物模組300D。置物模組300可具有防呆結構。舉例而言，置物模組300可具有插銷或者具有對應於容器的結構以定位置物模組300及容器，藉此防止置物模組300裝設錯誤或容器擺放錯誤。 The storage module 300 is used to place containers for samples, containers for extracted genetic substances, and extraction pipette tips. The containers for samples can be used to hold original liquid samples that have not yet been extracted. The extraction pipette tips can be installed in the later-described pipette module 700 for extraction. The storage module 300 can sequentially place containers for samples, extraction pipette tips, and containers for extracted genetic substances in the direction toward the extraction module 200. In other words, the container for extracted genetic substances is closest to the extraction module 200, so that the extracted genetic substances can be moved to the container in the shortest distance, thereby reducing the risk of contamination during the pipetting process. The storage module 300 can have different structures according to different sample types. For example, FIG. 3A to FIG. 3D are storage modules 300 suitable for different samples, FIG. 3A is a storage module 300A suitable for 10 ml of serum or plasma, FIG. 3B is a storage module 300B suitable for wax blocks (such as FFPE), FIG. 3C is a storage module 300C suitable for viruses or blood, and FIG. 3D is a storage module 300D suitable for 5 ml of serum or plasma. The storage module 300 may have a foolproof structure. For example, the storage module 300 may have a latch or a structure corresponding to a container to position the storage module 300 and the container, thereby preventing the storage module 300 from being installed incorrectly or the container from being placed incorrectly.
擴增前定量模組400用以對萃取完成的遺傳物質進行定量。在特定生化分析或應用中，有時在進行擴增反應前需要對樣品中的遺傳物質進行定量分析。擴增前定量模組400可為光學定量模組。可藉由後述之吸量模組700將放置於置物模組300的萃取完成的遺傳物質移動至擴增前定量模組400進行光學定量。擴增前定量模組400裝設有LED光源、濾光片及發光二極體，但不以此為限。舉例而言，擴增前定量模組400內建475nm的激發光過濾片與525nm的散射光過濾片，透過特定波長對遺傳物質進行量測，並使用內建軟體建立檢量線來對遺傳物質進行定量。 The pre-expansion quantitative module 400 is used to quantify the extracted genetic substances. In certain biochemical analyses or applications, it is sometimes necessary to quantify the genetic substances in the sample before the expansion reaction. The pre-expansion quantitative module 400 can be an optical quantitative module. The extracted genetic substances placed in the storage module 300 can be moved to the pre-expansion quantitative module 400 for optical quantification by the later-described pipetting module 700. The pre-expansion quantitative module 400 is equipped with an LED light source, a filter, and a light-emitting diode, but is not limited thereto. For example, the pre-expansion quantitative module 400 has a built-in 475nm excitation light filter and a 525nm scattered light filter, which measures genetic substances at specific wavelengths and uses built-in software to establish calibration curves to quantify genetic substances.
擴增樣品準備模組500用以將萃取完成的遺傳物質配製成適用於擴增反應的溶液。擴增樣品準備模組500可包含擴增試劑區510與擴增樣品放置區520。擴增試劑區510可用以放置用於擴增反應的試劑，例如聚合酶、dNTP、引子及緩衝液。擴增樣品放置區520可用以放置配製完成的適用於擴增反應的溶液。可藉由後述之吸量模組700將放置於置物模組300的萃取完成的遺傳物質移動至擴增樣品放置區520，再藉由吸量模組700 將放置於擴增試劑區510的試劑添加至萃取完成的遺傳物質中，配製成適用於擴增反應的溶液。配製完成的溶液可從自動化樣品準備系統10中取出，進行後續擴增反應或保存。 The expansion sample preparation module 500 is used to prepare the extracted genetic material into a solution suitable for the expansion reaction. The expansion sample preparation module 500 may include an expansion reagent area 510 and an expansion sample placement area 520. The expansion reagent area 510 may be used to place reagents used for the expansion reaction, such as polymerase, dNTP, primers and buffer. The expansion sample placement area 520 may be used to place the prepared solution suitable for the expansion reaction. The extracted genetic material placed in the storage module 300 can be moved to the expansion sample placement area 520 by the pipette module 700 described later, and then the reagent placed in the expansion reagent area 510 is added to the extracted genetic material by the pipette module 700 to prepare a solution suitable for the expansion reaction. The prepared solution can be taken out from the automated sample preparation system 10 for subsequent expansion reaction or storage.
非萃取用吸量管尖盛裝模組600用以盛裝非萃取用吸量管尖。非萃取用吸量管尖可用於與萃取無關的液體混合或移液。換言之，放置於置物模組300的萃取用吸量管尖可用於在樣品準備模組100、萃取模組200與置物模組300中的液體混合或移液，放置於非萃取用吸量管尖盛裝模組600的非萃取用吸量管尖可用於在置物模組300、擴增前定量模組400與擴增樣品準備模組500中的液體混合或移液。將萃取用吸量管尖與非萃取用吸量管尖區分開使用可減少在單一程序中吸量模組700移動的距離，可降低吸量模組700在裝設萃取管尖或移動的過程中造成汙染的風險。 The non-extraction pipette tip holding module 600 is used to hold non-extraction pipette tips. Non-extraction pipette tips can be used to mix or transfer liquids that are not related to extraction. In other words, the extraction pipette tips placed in the storage module 300 can be used to mix or transfer liquids in the sample preparation module 100, the extraction module 200 and the storage module 300, and the non-extraction pipette tips placed in the non-extraction pipette tip holding module 600 can be used to mix or transfer liquids in the storage module 300, the pre-expansion quantitative module 400 and the expansion sample preparation module 500. Separating the extraction pipette tips from the non-extraction pipette tips can reduce the distance that the pipette module 700 moves in a single procedure, thereby reducing the risk of contamination of the pipette module 700 during installation of the extraction pipette tip or during movement.
吸量模組700用以移動到置物模組300裝設萃取用吸量管尖以在樣品準備模組100、萃取模組200及置物模組300中進行液體混合或移液，或者用以移動到非萃取用吸量管尖盛裝模組600裝設非萃取用吸量管尖以在置物模組300、擴增前定量模組400及擴增樣品準備模組500中進行液體混合或移液。吸量模組700可透過來回吸吐的方式進行液體混合。吸量模組700可透過自動偵測或手動設定液體的體積，並依據液體體積進行來回吸吐，使液體進行全面性的混合。相較於攪拌混合，依據液體體 積進行來回吸吐的混合方式可使液體混合更加均勻，並可避免因攪拌造成碰撞而損壞。 The pipette module 700 is used to move to the storage module 300 to install the extraction pipette tip to mix or transfer liquids in the sample preparation module 100, the extraction module 200 and the storage module 300, or to move to the non-extraction pipette tip holding module 600 to install the non-extraction pipette tip to mix or transfer liquids in the storage module 300, the pre-expansion quantitative module 400 and the expansion sample preparation module 500. The pipette module 700 can mix liquids by sucking and spitting back and forth. The pipette module 700 can automatically detect or manually set the volume of the liquid, and suck and spit back and forth according to the liquid volume to mix the liquid comprehensively. Compared with stirring, the mixing method of sucking and spitting back and forth according to the volume of the liquid can make the liquid mix more evenly and avoid damage caused by collision caused by stirring.
吸量模組700可包含第一吸量模組710及第二吸量模組720。第一吸量模組710的移動範圍A可包含樣品準備模組100、萃取模組200與置物模組300。第一吸量模組710可移動到置物模組300裝設萃取用吸量管尖以在樣品準備模組100、萃取模組200及置物模組300中進行液體混合或移液。第二吸量模組720的移動範圍B可包含置物模組300、擴增前定量模組400、擴增樣品準備模組500與非萃取用吸量管尖盛裝模組600。第二吸量模組720可移動到非萃取用吸量管尖盛裝模組600裝設非萃取用吸量管尖以在置物模組300、擴增前定量模組400及擴增樣品準備模組500中進行液體混合或移液。第一吸量模組710與第二吸量模組720可分別在不同區域內移動，可減少單一吸量模組的移動距離，藉此可降低在裝設萃取管尖或移動的過程中造成汙染的風險。 The pipetting module 700 may include a first pipetting module 710 and a second pipetting module 720. The moving range A of the first pipetting module 710 may include the sample preparation module 100, the extraction module 200 and the storage module 300. The first pipetting module 710 may be moved to the storage module 300 to install the extraction pipette tip to mix or transfer liquids in the sample preparation module 100, the extraction module 200 and the storage module 300. The moving range B of the second pipetting module 720 may include the storage module 300, the pre-expansion quantitative module 400, the expansion sample preparation module 500 and the non-extraction pipette tip containing module 600. The second pipette module 720 can be moved to the non-extraction pipette tip holding module 600 to install the non-extraction pipette tip to mix or pipette liquids in the storage module 300, the pre-expansion quantitative module 400, and the expansion sample preparation module 500. The first pipette module 710 and the second pipette module 720 can move in different areas respectively, which can reduce the moving distance of a single pipette module, thereby reducing the risk of contamination during the installation of the extraction tip or the movement process.
萃取模組200、樣品準備模組100及置物模組300可沿第一方向依序排列，擴增前定量模組400、擴增樣品放置區520、擴增試劑區510與非萃取用吸量管尖盛裝模組600可沿第二方向依序排列，第一方向可垂直第二方向。藉由此排列方式，在吸量模組700從非萃取用吸量管尖盛裝模組600裝設非萃取用吸量管尖、移動至擴增試劑區510吸取試劑再添加至放置於擴增樣品放 置區520的遺傳物質的過程中，可減少移動距離，藉此可降低吸量模組700在裝設萃取管尖或移動的過程中造成汙染的風險。 The extraction module 200, the sample preparation module 100 and the storage module 300 can be arranged in sequence along the first direction, and the pre-expansion quantitative module 400, the expanded sample placement area 520, the expanded reagent area 510 and the non-extraction pipette tip holding module 600 can be arranged in sequence along the second direction, and the first direction can be perpendicular to the second direction. With this arrangement, the pipette module 700 can reduce the moving distance in the process of installing the non-extraction pipette tip from the non-extraction pipette tip holding module 600, moving to the expanded reagent area 510 to absorb the reagent and then adding it to the genetic material placed in the expanded sample placement area 520, thereby reducing the risk of contamination caused by the pipette module 700 during the installation of the extraction tip or the movement.
自動化樣品準備系統10可更包含廢棄物收集模組800。廢棄物收集模組800可用以收集使用過的吸量管尖或收集廢液。 The automated sample preparation system 10 may further include a waste collection module 800. The waste collection module 800 may be used to collect used pipette tips or waste liquid.
自動化樣品準備系統10可更包含殼體900，殼體900可包含開口910。樣品準備模組100、萃取模組200、置物模組300、擴增前定量模組400、擴增樣品準備模組500、非萃取用吸量管尖盛裝模組600與吸量模組700可設置於殼體900內，擴增前定量模組400、擴增樣品準備模組500與非萃取用吸量管尖盛裝模組600可介於置物模組300與開口910之間。殼體900可更包含門板以覆蓋開口910。此排列方式可方便從開口910拿取配製完成的適用於擴增反應的溶液，可避免接觸樣品準備模組100、萃取模組200或置物模組300，藉此可降低觸碰造成的汙染或損壞的風險。 The automated sample preparation system 10 may further include a housing 900, and the housing 900 may include an opening 910. The sample preparation module 100, the extraction module 200, the storage module 300, the pre-expansion quantitative module 400, the expansion sample preparation module 500, the non-extraction pipette tip holding module 600, and the pipette module 700 may be disposed in the housing 900, and the pre-expansion quantitative module 400, the expansion sample preparation module 500, and the non-extraction pipette tip holding module 600 may be located between the storage module 300 and the opening 910. The housing 900 may further include a door panel to cover the opening 910. This arrangement makes it easy to take the prepared solution suitable for the expansion reaction from the opening 910, and avoids contact with the sample preparation module 100, the extraction module 200 or the storage module 300, thereby reducing the risk of contamination or damage caused by contact.
自動化樣品準備系統10可更包含影像辨識模組920。影像辨識模組920可設置於殼體900內。影像辨識模組920可用以辨識盛裝樣品的容器或盛裝的遺傳物質的容器上的標籤或標示。標籤或標示可為文字、數字或條碼。舉例而言，當盛裝樣品的容器為採血管時，影像辨識模組920可辨識採血管上的標籤並將資訊傳回電腦，以便數據整理及分析。影像辨識模組920亦 可辨識耗材的擺放與排列。舉例而言，影像辨識模組920可辨識非萃取用吸量管尖盛裝模組600中非萃取用吸量管尖的數量、擺放與排列，使吸量模組700可移動到正確的位置裝設吸量管尖，或是在吸量管尖不足時發出警訊。 The automated sample preparation system 10 may further include an image recognition module 920. The image recognition module 920 may be disposed in the housing 900. The image recognition module 920 may be used to recognize labels or marks on containers containing samples or containers containing genetic substances. The labels or marks may be text, numbers, or bar codes. For example, when the container containing the sample is a blood collection tube, the image recognition module 920 may recognize the label on the blood collection tube and transmit the information back to the computer for data collation and analysis. The image recognition module 920 may also recognize the placement and arrangement of consumables. For example, the image recognition module 920 can identify the number, placement and arrangement of non-extraction pipette tips in the non-extraction pipette tip storage module 600, so that the pipette module 700 can move to the correct position to install the pipette tips, or issue an alarm when the pipette tips are insufficient.
自動化樣品準備系統10可更包含紫外光滅菌模組930。紫外光滅菌模組930可設置於殼體900內。紫外光滅菌模組930可用以對樣品準備模組100、萃取模組200、置物模組300、擴增前定量模組400、擴增樣品準備模組500、非萃取用吸量管尖盛裝模組600與吸量模組700進行滅菌。紫外光滅菌模組930可包含紫外光燈管，可裝設於殼體900內部的頂部或是可使紫外光照射到各模組的任意位置。紫外光滅菌模組930可確保在放入樣品時殼體900內處於無菌的狀態。 The automated sample preparation system 10 may further include an ultraviolet sterilization module 930. The ultraviolet sterilization module 930 may be disposed in the housing 900. The ultraviolet sterilization module 930 may be used to sterilize the sample preparation module 100, the extraction module 200, the storage module 300, the pre-expansion quantitative module 400, the expansion sample preparation module 500, the non-extraction pipette tip containing module 600 and the pipette module 700. The ultraviolet sterilization module 930 may include an ultraviolet light tube, which may be installed at the top of the housing 900 or may allow ultraviolet light to irradiate any position of each module. The ultraviolet sterilization module 930 may ensure that the housing 900 is in a sterile state when the sample is placed.
以下描述將樣品放入自動化樣品準備系統10到取出的一例。首先，在樣品為液態的情況下，將盛裝有樣品的容器放置於置物模組300，樣品經由第一吸量模組710移動至樣品準備模組100進行稀釋或加熱處理，成為可用於萃取的形態。在樣品為固態的情況下，將樣品直接放置於萃取試劑條210中位於樣品準備模組100的管體中進行稀釋或加熱處理，成為可用於萃取的形態。接著，放置於樣品準備模組100的待萃取樣品經由第一吸量模組710移動至萃取模組200，依序與萃取試劑條210中的各反應試劑混合以進行萃取反應。萃取完成的樣品經由第一吸量模 組710移動至放置於置物模組300的容器中。前述過程由第一吸量模組710裝設放置於置物模組300的萃取用吸量管尖來進行液體混合或移液。 The following describes an example of placing a sample into the automated sample preparation system 10 and taking it out. First, when the sample is liquid, the container containing the sample is placed in the storage module 300, and the sample is moved to the sample preparation module 100 via the first pipette module 710 for dilution or heating treatment to become a form that can be used for extraction. When the sample is solid, the sample is directly placed in the tube of the extraction reagent strip 210 located in the sample preparation module 100 for dilution or heating treatment to become a form that can be used for extraction. Then, the sample to be extracted placed in the sample preparation module 100 is moved to the extraction module 200 via the first pipette module 710, and is sequentially mixed with each reaction reagent in the extraction reagent strip 210 to perform an extraction reaction. The extracted sample is moved to the container placed in the storage module 300 through the first pipette module 710. The above process is performed by the first pipette module 710 equipped with the extraction pipette tip placed in the storage module 300 to mix or transfer liquids.
接著，若需要進行擴增前定量，則將放置於置物模組300的萃取完成的樣品經由第二吸量模組720移動至擴增前定量模組400進行定量。接著，視定量結果或是在不需進行擴增前定量的情況下，將放置於置物模組300的萃取完成的樣品經由第二吸量模組720移動至擴增樣品準備模組500的擴增樣品放置區520。藉由第二吸量模組720將放置於擴增樣品準備模組500的擴增試劑區510的試劑添加至萃取完成的樣品中，配製成適用於擴增反應的溶液。配製完成的溶液可從開口910取出，進行後續擴增反應或保存。前述過程由第二吸量模組720裝設放置於非萃取用吸量管尖盛裝模組600的非萃取用吸量管尖來進行液體混合或移液。 Next, if quantification before expansion is required, the extracted sample placed in the storage module 300 is moved to the pre-expansion quantification module 400 for quantification via the second pipetting module 720. Next, depending on the quantification result or if quantification before expansion is not required, the extracted sample placed in the storage module 300 is moved to the expanded sample placement area 520 of the expanded sample preparation module 500 via the second pipetting module 720. The reagent placed in the expanded reagent area 510 of the expanded sample preparation module 500 is added to the extracted sample by the second pipetting module 720 to prepare a solution suitable for expansion reaction. The prepared solution can be taken out from the opening 910 for subsequent expansion reaction or storage. The aforementioned process is performed by the second pipetting module 720 installing a non-extraction pipette tip placed in the non-extraction pipette tip holding module 600 to mix or pipette liquids.
根據本發明一實施例的自動化樣品準備系統，將樣品前處理、萃取、擴增前定量、配製擴增溶液整合於一個系統中。自動化樣品準備系統的樣品準備模組除了液體樣品以外，亦可對如蠟塊之固體樣品進行前處理。自動化樣品準備系統的吸量模組可透過來回吸吐的方式使液體進行全面性的混合，相較於攪拌混合，可使液體混合更加均勻，並可避免因攪拌造成碰撞而損壞。自動化樣品準備系統中各模組的排列方式可減少吸量模組在各模 組間的移動距離，藉此降低在移動過程中造成汙染或碰撞損壞的風險。藉由將各程序自動化來取代人為操作，可簡化操作、降低時間人力成本、提升效率，且藉由標準化的流程可減少人為誤差、提高可靠性，更重要的是，可大幅降低受到汙染的風險。 According to an automated sample preparation system of an embodiment of the present invention, sample pretreatment, extraction, pre-expansion quantification, and preparation of expansion solution are integrated into one system. In addition to liquid samples, the sample preparation module of the automated sample preparation system can also pre-treat solid samples such as wax blocks. The pipetting module of the automated sample preparation system can fully mix the liquid by aspirating and spitting back and forth, which can make the liquid mix more uniformly compared to stirring and mixing, and can avoid collision and damage caused by stirring. The arrangement of the modules in the automated sample preparation system can reduce the moving distance of the pipetting module between the modules, thereby reducing the risk of contamination or collision damage during the movement process. By automating each process to replace manual operations, operations can be simplified, time and labor costs can be reduced, and efficiency can be improved. Standardized processes can reduce human errors, improve reliability, and more importantly, significantly reduce the risk of contamination.
雖然本發明以前述之實施例揭露如上，然其並非用以限定本發明。在不脫離本發明之精神和範圍內，所為之更動與潤飾，均屬本發明之專利保護範圍。關於本發明所界定之保護範圍請參考所附之申請專利範圍。 Although the present invention is disclosed as above by the aforementioned embodiments, it is not intended to limit the present invention. Any changes and modifications made within the spirit and scope of the present invention are within the scope of patent protection of the present invention. Please refer to the attached patent application for the scope of protection defined by the present invention.
10:自動化樣品準備系統 10: Automated sample preparation system
100:樣品準備模組 100: Sample preparation module
200:萃取模組 200: Extraction module
300:置物模組 300: Storage module
400:擴增前定量模組 400: Expand the quantitative module before
500:擴增樣品準備模組 500: Expanded sample preparation module
510:擴增試劑區 510: Expanded reagent area
520:擴增樣品放置區 520: Expanded sample placement area
600:非萃取用吸量管尖盛裝模組 600: Non-extraction pipette tip holder module
700:吸量模組 700: Suction module
710:第一吸量模組 710: First suction module
720:第二吸量模組 720: Second suction module
800:廢棄物收集模組 800: Waste collection module
900:殼體 900: Shell
910:開口 910: Open mouth
920:影像辨識模組 920: Image recognition module
930:紫外光滅菌模組 930: UV sterilization module
A:第一吸量模組的移動範圍 A: The moving range of the first suction module
B:第二吸量模組的移動範圍 B: Moving range of the second suction module
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| JP2020534792A (en) | 2017-07-21 | 2020-12-03 | シージーン アイエヌシー | Magnetic bead transfer module, automated system including the module, and nucleic acid extraction method using the module |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020534792A (en) | 2017-07-21 | 2020-12-03 | シージーン アイエヌシー | Magnetic bead transfer module, automated system including the module, and nucleic acid extraction method using the module |
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